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Rationale: Hospitalized patients with acute-on-chronic hypercapnic respiratory failure due to obesity hypoventilation syndrome (OHS) have increased short-term mortality. It is unknown whether prescribing empiric positive airway pressure (PAP) at the time of hospital discharge reduces mortality compared with waiting for an outpatient evaluation (i.e., outpatient sleep study and outpatient PAP titration).Objectives: An international, multidisciplinary panel of experts developed clinical practice guidelines on OHS for the American Thoracic Society. The guideline panel asked whether hospitalized adult patients with acute-on-chronic hypercapnic respiratory failure suspected of having OHS, in whom the diagnosis has not yet been made, should be discharged from the hospital with or without empiric PAP treatment until the diagnosis of OHS is either confirmed or ruled out.Methods: A systematic review with individual patient data meta-analyses was performed to inform the guideline panel's recommendation. Grading of Recommendations, Assessment, Development, and Evaluation was used to summarize evidence and appraise quality.Results: The literature search identified 2,994 articles. There were no randomized trials. Ten studies met a priori study selection criteria, including two nonrandomized comparative studies and eight nonrandomized noncomparative studies. Individual patient data on hospitalized patients who survived to hospital discharge were obtained from nine of the studies and included a total of 1,162 patients (1,043 discharged with PAP and 119 discharged without PAP). Empiric noninvasive ventilation was prescribed in 91.5% of patients discharged on PAP, and the remainder received empiric continuous PAP. Discharge with PAP reduced mortality at 3 months (relative risk 0.12, 95% confidence interval 0.05-0.30, risk difference -14.5%). Certainty in the estimated effects was very low.Conclusions: Hospital discharge with PAP reduces mortality following acute-on-chronic hypercapnic respiratory failure in patients with OHS or suspected of having OHS. Well-designed clinical trials are needed to confirm this finding.

Spanish Sleep Network., [Rationale] Obesity hypoventilation syndrome (OHS) has been associated with cardiac dysfunction. However, randomized trials assessing the impact of long-term noninvasive ventilation (NIV) or continuous positive airway pressure (CPAP) on cardiac structure and function assessed by echocardiography are lacking. Rationale: Obesity hypoventilation syndrome (OHS) has been associated with cardiac dysfunction. However, randomized trials assessing the impact of long-term noninvasive ventilation (NIV) or continuous positive airway pressure (CPAP) on cardiac structure and function assessed by echocardiography are lacking., [Objectives] In a prespecified secondary analysis of the largest multicenter randomized controlled trial of OHS (Pickwick Project; N = 221 patients with OHS and coexistent severe obstructive sleep apnea), we compared the effectiveness of three years of NIV and CPAP on structural and functional echocardiographic changes., [Methods] At baseline and annually during three sequential years, patients underwent transthoracic two-dimensional and Doppler echocardiography. Echocardiographers at each site were blinded to the treatment allocation. Statistical analysis was performed using a linear mixed-effects model with a treatment group and repeated measures interaction to determine the differential effect between CPAP and NIV. Measurements and Main Results: A total of 196 patients were analyzed: 102 were treated with CPAP and 94 were treated with NIV. Systolic pulmonary artery pressure decreased from 40.5 ± 1.47 mm Hg at baseline to 35.3 ± 1.33 mm Hg at three years with CPAP, and from 41.5 ± 1.56 mm Hg to 35.5 ± 1.42 with NIV (P, [Conclusions] In patients with OHS who have concomitant severe obstructive sleep apnea, long-term treatment with NIV and CPAP led to similar degrees of improvement in pulmonary hypertension and left ventricular diastolic dysfunction.

Background: The purpose of this guideline is to optimize evaluation and management of patients with obesity hypoventilation syndrome (OHS). Methods: A multidisciplinary panel identified and prioritized five clinical questions. The panel performed systematic reviews of available studies (up to July 2018) and followed the Grading of Recommendations, Assessment, Development, and Evaluation evidence-to-decision framework to develop recommendations. All panel members discussed and approved the recommendations. Recommendations: After considering the overall very low quality of the evidence, the panel made five conditional recommendations. We suggest that: 1) clinicians use a serum bicarbonate level

Obesity is a major risk factor for the development of obstructive sleep apnea (OSA) and obesity hypoventilation syndrome (OHS), which manifest as intermittent hypercapnia and sustained plus intermittent hypercapnia, respectively. In this study, we investigated whether CO2 affects adipocyte differentiation (adipogenesis) and maturation (hypertrophy). Human visceral or subcutaneous preadipocytes were grown to confluence and then induced to differentiate to adipocytes under hypocapnia, normocapnia, and hypercapnia with or without hypoxia. Adipogenesis was also induced under intermittent or sustained hypercapnia. Differentiated adipocytes were maintained to maturity under normocapnia or hypercapnia. Our main findings are as follows: (1) hypercapnia accelerated adipogenesis in visceral and subcutaneous preadipocytes, whereas hypocapnia inhibited adipogenesis; (2) hypercapnia did not affect adipocyte hypertrophy; (3) hypercapnia-accelerated adipogenesis was independent of extracellular acidosis, oxygen concentr...

Prevalence studies have shown heterogeneous use of home mechanical ventilation in different conditions, with a marked increase in uptake especially in users of noninvasive ventilation. Although randomized controlled trials have examined noninvasive ventilation in acute exacerbations of chronic obstructive pulmonary disease, for weaning from invasive ventilation and for postextubation respiratory failure, the evidence base for long-term noninvasive ventilation and comparisons with invasive ventilation are less well developed. The combination of noninvasive ventilation and cough-assist devices has reduced the indications for tracheotomy ventilation in some situations (e.g., Duchenne muscular dystrophy, spinal muscular atrophy, myopathies, and amyotrophic lateral sclerosis) and has also prolonged survival. Several excellent overviews have been written on the history of home mechanical ventilation and its evolution from negative pressure to positive pressure techniques, including a systematic review of outcomes. This review, instead, will cover recent trials, trends in the field, outcomes, and safety. Because the greatest growth has been in home noninvasive ventilation, this will be the main focus of this article.

Comparisons of home mechanical ventilation services have demonstrated considerable regional variation in patient populations managed with this therapy. The respiratory care practices used to support individuals receiving assisted ventilation also appear to vary, but they are not well described. It is uncertain whether differences in the approach to care could influence health outcomes for individuals receiving assisted ventilation.We sought to identify and describe the respiratory care practices of home ventilation providers in two different regions and determine whether care practice differences influence health-related quality of life.We conducted a cross-national survey of individuals receiving assisted ventilation managed by two statewide home mechanical ventilation providers, one in Victoria, Australia, and the other in British Columbia, Canada. The survey was used to evaluate care practices, functional and physical measures, socioeconomic attributes, and health-related quality of life.Overall, 495 individuals receiving assisted ventilation (57.2%) responded to the survey. Responders had clinical attributes similar to those of nonresponders. The Canadian population had a greater proportion of individuals with neuromuscular disorders and lesser percentages with obesity hypoventilation syndrome and chronic obstructive pulmonary disease. We also found marked differences in the reported care practices in Canada that were not fully explained by population differences. Subjects in the Canadian sample were more likely than their Australian counterparts to use invasive mechanical ventilation (24.2% vs. 2.5%; P 0.001), to use routine airway clearance techniques (28.9% vs. 14.8%; P 0.001), and to have had home implementation of noninvasive ventilation (39.9% vs. 3.6%; P 0.001). Subjects in the Australian population were more likely than those in Canada to have undergone polysomnography to evaluate their ventilatory support (93.9% vs. 37.4%; P 0.001). There was no difference in summary measures of health-related quality of life between the two sites. In a multivariable regression model, age, ability to perform activities of daily living, physical function, employment, and household income were all independently associated with health-related quality of life, but neither geographic location (Canada vs. Australia) nor underlying diagnosis were significant factors in the model.In two cohorts of individuals receiving assisted ventilation, one in Australia and the other in Canada, we found marked differences in both the care practices employed and the populations served. Despite these regional differences, measures of health-related quality of life were not different. Further research is required to examine costly or burdensome interventions that are currently used routinely in the management of individuals receiving assisted ventilation.

The progression from obesity and obstructive sleep apnea to obesity with hypoventilation and daytime hypercapnia may relate to features of sleep-disordered breathing events that affect loading and unloading of carbon dioxide.To determine whether the wake Pco2 increases over time in untreated obstructive sleep apnea, and whether that increase is explained by changes in sleep-disordered breathing event duration, interevent duration, or postevent ventilation amplitude.We selected 14 adults who had two polysomnographic studies more than 1 year apart because of untreated or suboptimally treated moderate to severe obstructive sleep apnea. Demographic and polysomnographic data were reviewed for both sets of studies, including the evening wake end-tidal CO2, the ratio of mean event to mean interevent duration (subsuming apneas and hypopneas), and the ratio of mean post- to preevent breath amplitude.The mean (SD) wake end-tidal Pco2 increased between studies from 35.9 (4.2) to 39.5 (3.9) mm Hg (P 0.005). The wake end-tidal CO2 correlated inversely with the post- to pre-event breath amplitude and positively with the ratio of mean event to mean interevent duration and with body mass index. However, those three variables were not significantly changed between the two studies. The wake end-tidal CO2 did not correlate with the apnea-hypopnea index or age. There was a significant increase in bicarbonate level between studies (median, 24.0-26.5 mmol/L; P = 0.01).In our study cohort, wake end-tidal CO2 correlated with body mass index and features of sleep apnea that influence the balance of loading and unloading of CO2. However, those features remained fixed over time, even as the wake Pco2 and bicarbonate levels increased with untreated sleep apnea.

The prevalence of obesity hypoventilation syndrome and obstructive sleep apnea are increasing rapidly in the United States in parallel with the obesity epidemic. As the pathogenesis of this chronic illness is better understood, effective evidence-based therapies are being deployed to reduce morbidity and mortality. Nevertheless, patients with obesity hypoventilation still fall prey to at least four avoidable types of therapeutic errors, especially at the time of hospitalization for respiratory or cardiovascular decompensation: (1) patients with obesity hypoventilation syndrome may develop acute hypercapnia in response to administration of excessive supplemental oxygen; (2) excessive diuresis for peripheral edema using a loop diuretic such as furosemide exacerbates metabolic alkalosis, thereby worsening daytime hypoventilation and hypoxemia; (3) excessive or premature pharmacological treatment of psychiatric illnesses can exacerbate sleep-disordered breathing and worsen hypercapnia, thereby exacerbating psychiatric symptoms; and (4) clinicians often erroneously diagnose obstructive lung disease in patients with obesity hypoventilation, thereby exposing them to unnecessary and potentially harmful medications, including β-agonists and corticosteroids. Just as literary descriptions of pickwickian syndrome have given way to greater understanding of the pathophysiology of obesity hypoventilation, clinicians might exercise caution to consider these potential pitfalls and thus avoid inflicting unintended and avoidable complications.

The incidence of obesity hypoventilation syndrome (OHS) may be increasing in parallel with the present obesity epidemic. Despite extensive noninvasive ventilation (NIV) and continuous positive airway pressure (CPAP) use in patients with OHS, information regarding efficacy is limited.We performed a large, multicenter randomized controlled study to determine the comparative efficacy of NIV, CPAP, and lifestyle modification (control group) using daytime PaCO2 as the main outcome measure.Sequentially screened patients with OHS with severe sleep apnea were randomized into the above-mentioned groups for a 2-month follow up. Arterial blood gas parameters, clinical symptoms, health-related quality-of-life assessments, polysomnography, spirometry, 6-minute-walk distance, dropouts, compliance, and side effects were evaluated. Statistical analysis was performed using intention-to-treat analysis, although adjustments for CPAP and NIV compliance were also analyzed.In total, 351 patients were selected, and 221 were randomized. NIV yielded the greatest improvement in PaCO2 and bicarbonate, with significant differences relative to the control group but not relative to the CPAP group. In the CPAP group, PaCO2 improvement was significantly different than in the control group only after CPAP compliance adjustment. Additionally, clinical symptoms and polysomnographic parameters improved similarly with NIV and CPAP relative to the control. However, some health-related quality-of-life assessments, the spirometry, and 6-minute-walk distance results improved more with NIV than with CPAP. Dropouts were similar between groups, and compliance and secondary effects were similar between NIV and CPAP.NIV and CPAP were more effective than lifestyle modification in improving clinical symptoms and polysomnographic parameters, although NIV yielded better respiratory functional improvements than did CPAP. Long-term studies must demonstrate whether this functional improvement has relevant implications. Clinical trial registered with www.clinicaltrials.gov (NCT01405976).

The purpose of this workshop was to identify knowledge gaps in the perioperative management of obstructive sleep apnea (OSA) and obesity hypoventilation syndrome (OHS). A single-day meeting was held at the American Thoracic Society Conference in May, 2016, with representation from many specialties, including anesthesiology, perioperative medicine, sleep, and respiratory medicine. Further research is urgently needed as we look to improve health outcomes for these patients and reduce health care costs. There is currently insufficient evidence to guide screening and optimization of OSA and OHS in the perioperative setting to achieve these objectives. Patients who are at greatest risk of respiratory or cardiac complications related to OSA and OHS are not well defined, and the effectiveness of monitoring and other interventions remains to be determined. Centers involved in sleep research need to develop collaborative networks to allow multicenter studies to address the knowledge gaps identified below.

Obesity hypoventilation syndrome describes the association between obesity and the development of chronic daytime alveolar hypoventilation. This syndrome arises from a complex interaction between sleep-disordered breathing, diminished respiratory drive, and obesity-related respiratory impairment, and is associated with significant morbidity and mortality. Therapy directed toward reversing these abnormalities leads to improved daytime breathing, with available treatment options including positive pressure therapy, weight loss, and pharmacological management. However, a lack of large-scale, well-designed studies evaluating these various therapies has limited the development of evidence-based treatment recommendations. Although treatment directed toward improving sleep-disordered breathing is usually effective, not all patients tolerate mask ventilation and awake hypercapnia may persist despite effective use. In the longer term, weight loss is desirable, but data on the success and sustainability of this approach in obesity hypoventilation are lacking. The review outlines the major mechanisms believed to underlie the development of hypoventilation in this subgroup of obese patients, their clinical presentation, and current therapy options.

Obesity hypoventilation syndrome (OHS) is characterized by obesity, daytime hypercapnia, and sleep-disordered breathing in the absence of significant lung or respiratory muscle disease. Compared with eucapnic morbidly obese patients and eucapnic patients with sleep-disordered breathing, patients with OHS have increased health care expenses and are at higher risk of developing serious cardiovascular disease leading to early mortality. Despite the significant morbidity and mortality associated with this syndrome, diagnosis and institution of effective treatment occur late in the course of the syndrome. Given that the prevalence of extreme obesity has increased considerably, it is likely that clinicians will encounter patients with OHS in their clinical practice. Therefore maintaining a high index of suspicion can lead to early recognition and treatment reducing the high burden of morbidity and mortality and related health care expenditure associated with undiagnosed and untreated OHS. In this review we define the clinical characteristics of the syndrome and review the pathophysiology, morbidity, and mortality associated with it. Last, we discuss currently available treatment modalities.

Prevention of acute hypercapnia during obstructive events in obstructive sleep apnea requires a balance between carbon dioxide (CO(2)) loading during the event and CO(2) unloading in the interevent period. Earlier studies have demonstrated that acute CO(2) retention may occur despite high interevent ventilation when the interevent duration is short relative to the duration of the preceding event. The present study examines the relationship between apnea and interapnea durations and relates this assessment of ventilatory periodicity to the degree of chronic hypercapnia in subjects with severe sleep apnea. A total of 18 subjects with sleep apnea (> 40 apnea/hour; chronic awake Pa(CO2) 36-62 mm Hg) and without underlying lung disease underwent polysomnography. For each event, apnea duration, interapnea duration, and apnea/interapnea duration ratio were determined. No relationship was observed between chronic Pa(CO2) and mean apnea or interapnea duration (p > 0.1). However, Pa(CO2) was directly related to apnea/interapnea duration ratio (r = 0.48; p < 0.05) such that with increasing chronic hypercapnia the interapnea duration shortens relative to the apnea duration. The present study suggests that control of the interapnea ventilatory duration relative to the duration of the preceding apnea, is an important component of the integrated ventilatory response to CO(2) loading during apnea and may contribute toward the development and/or maintenance of chronic hypercapnia in obstructive sleep apnea/hypopnea syndrome.

Rationale: Among respiratory events which may occur during nocturnal non-invasive ventilation (NIV), differentiating between central and obstructive events requires appropriate indicators of respiratory effort. Objective: To assess pulse transit time (PTT) as an indicator of respiratory effort under NIV in comparison with esophageal pressure (Pes). Methods: 1: During wake period, PTT was compared to Pes during spontaneous breathing and under NIV with or without induced leaks in 11 healthy individuals. 2: To evaluate the contribution of PTT vs Pes for differentiating central from obstructive respiratory events occurring under NIV during sleep in 10 patients with obesity hypoventilation syndrome (OHS). Results: 1: From spontaneous breathing to NIV without leaks, respiratory effort decreased significantly and with increasing level of leaks, there was a significant increase in respiratory effort. In both situations changes in PTT accurately reflected changes in Pes. 2: In OHS patients during nocturnal NIV, intraclass correlation coefficients between Pes and PTT were 0.970 for total number of events and 0.970 for percentage of central events. Conclusion: PTT accurately reflects the unloading of respiratory muscles induced by NIV and the increase in respiratory effort during NIV. PTT during sleep is also useful to differentiate central from obstructive respiratory events occurring under NIV. Clinical trial registration number: [NCT00983411][1]. [1]: /lookup/external-ref?link_type=CLINTRIALGOV&access_num=NCT00983411&atom=%2Ferj%2F40%2FSuppl_56%2F2850.atom

Rationale: Both obesity and obstructive sleep apnea (OSA) are risk factors for hypertension (HT) and chronic heart failure (CHF). The association between OSA and COPD (overlap syndrome) and the obesity hypoventilation syndrome (OHS) have been proposed as leading to enhanced cardiovascular risk. Methods: 3093 obese subjects (IMC>30kg/m2) referred for suspicion of OSA were prospectively assessed by sleep studies, lung function tests and blood gazes. For the whole group, mean age was 57±13 years with 66% of men, mean BMI: 36.8±6.2 kg/m2, 52.8% of the subjects being hypertensive and 3.23% suffering from CHF. 926 of the 3093 did not exhibit OSA or COPD. Results: In multivariate analysis, prevalent hypertension was associated with OSA (Odd ratio (OR): 1.23 (confidence intervals (CI): 1.04-1.45), p=0.015), ≥2 nocturia episodes per night (OR: 1.295 (CI: 1.10-1.52), p